Reference ID: 4668211
`
`HIGHLIGHTS OF PRESCRIBING INFORMATION
`These highlights do not include all the information needed to use
`Injectafer safely and effectively. See full prescribing information for
`Injectafer.
`
`INJECTAFER® (ferric carboxymaltose injection), for intravenous use
`Initial U.S. Approval: 2013
`
`------------------------------RECENT MAJOR CHANGES------------------------
`Warnings and Precautions, Symptomatic Hypophosphatemia. (5.2) 02/2020
`----------------------------INDICATIONS AND USAGE---------------------------
`Injectafer is an iron replacement product indicated for the treatment of iron
`deficiency anemia (IDA) in adult patients:
`• who have intolerance to oral iron or have had unsatisfactory response to
`oral iron, or
`• who have non-dialysis dependent chronic kidney disease.
`----------------------DOSAGE AND ADMINISTRATION-----------------------
`For patients weighing 50 kg (110 lb) or more: Give Injectaferin two doses
`separated by at least 7 days. Give each dose as 750 mg for a total cumulative
`dose of 1500 mg of iron per course.
`For patients weighing less than 50 kg (110 lb): Give Injectafer in two doses
`separated by at least 7 days and give each dose as 15 mg/kg body weight.
`Injectafer treatment may be repeated if iron deficiency anemia reoccurs. (2)
`
`---------------------DOSAGE FORMS AND STRENGTHS----------------------
`Injection: 750 mg iron / 15 mL single-dose vial (3)
`
`-------------------------------CONTRAINDICATIONS------------------------------
`Hypersensitivity to Injectafer or any of its inactive components. (4)
`
`-----------------------WARNINGS AND PRECAUTIONS------------------------
`Hypersensitivity reactions: Observe for signs and symptoms of
`•
`hypersensitivity during and after Injectafer administration for at least 30
`minutes and until clinically stable following completion of each
`administration. (5.1)
`Symptomatic Hypophosphatemia: Monitor serum phosphate levels in
`patients at risk for low serum phosphate who require a repeat course of
`treatment. (5.2)
`Hypertension: Monitor patients closely for signs and symptoms of
`hypertension following each Injectafer administration. (5.3)
`
`•
`
`•
`
`------------------------------ADVERSE REACTIONS-------------------------------
`The most common adverse reactions (>2%) are nausea, hypertension,
`flushing, hypophosphatemia, and dizziness. (6.1)
`
`To report SUSPECTED ADVERSE REACTIONS, contact American
`Regent at 1-800-734-9236 or FDA at 1-800-FDA-1088 or
`www.fda.gov/medwatch.
`
`-------------------------USE IN SPECIFIC POPULATIONS----------------------
`Lactation: Monitor breastfed infants for gastrointestinal toxicity. (8.2)
`
`See 17 for PATIENT COUNSELING INFORMATION and FDA-
`approved patient labeling.
`
` Revised: 9/2020
`
`____________________________________________________________________________________________________________
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`
`INDICATIONS AND USAGE
`1
`2 DOSAGE AND ADMINISTRATION
`2.1 Recommended Dosage
`2.2
`Preparation and Administration
`2.3 Repeat Treatment Monitoring Safety Assessment
`3 DOSAGE FORMS AND STRENGTHS
`4 CONTRAINDICATIONS
`5 WARNINGS AND PRECAUTIONS
`5.1 Hypersensitivity Reactions
`Symptomatic Hypophosphatemia
`5.2
`5.3 Hypertension
`Laboratory Test Alterations
`5.4
`6 ADVERSE REACTIONS
`6.1 Clinical Trials Experience
`6.2
`Post-marketing Experience
`8 USE IN SPECIFIC POPULATIONS
`Pregnancy
`8.1
`8.2
`Lactation
`8.4
`Pediatric Use
`8.5 Geriatric Use
`___________________________________________________________________________________________________________________________________
`
`10 OVERDOSAGE
`11 DESCRIPTION
`12 CLINICAL PHARMACOLOGY
`12.1 Mechanism of Action
`12.2 Pharmacodynamics
`12.3 Pharmacokinetics
`13 NONCLINICAL TOXICOLOGY
`13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility
`14 CLINICAL STUDIES
`14.1 Trial 1: Iron Deficiency Anemia in Patients Who are Intolerant to
`Oral Iron or Have Had Unsatisfactory Response to Oral Iron
`14.2 Trial 2: Iron Deficiency Anemia in Patients with Non-Dialysis
`Dependent Chronic Kidney Disease
`16 HOW SUPPLIED/STORAGE AND HANDLING
`17 PATIENT COUNSELING INFORMATION
`
`* Sections or subsections omitted from the full prescribing information are not
`listed.
`
`1
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`

`Reference ID: 4668211
`
`FULL PRESCRIBING INFORMATION
`
`INDICATIONS AND USAGE
`
`Injectafer is indicated for the treatment of iron deficiency anemia (IDA) in adult patients:
`
`• who have intolerance to oral iron or have had unsatisfactory response to oral iron, or
`• who have non-dialysis dependent chronic kidney disease.
`
` 1
`
` 2
`
`DOSAGE AND ADMINISTRATION
`
`2.1 Recommended Dosage
`Recommended dosage for patients weighing 50 kg (110 lb) or more: Give Injectafer in
`two doses separated by at least 7 days. Give each dose as 750 mg for a total cumulative
`dose not to exceed 1500 mg of iron per course.
`
`Recommended dosage for patients weighing less than 50 kg (110 lb): Give Injectafer in
`two doses separated by at least 7 days. Give each dose as 15 mg/kg body weight for a
`total cumulative dose not to exceed 1500 mg of iron per course.
`
`Each mL of Injectafer contains 50 mg of elemental iron.
`
`2.2 Preparation and Administration
`Administer Injectafer intravenously, either as an undiluted slow intravenous push or by
`infusion. When administered via infusion, dilute up to 750 mg of iron in no more than
`250 mL of sterile 0.9% sodium chloride injection, USP, such that the concentration of the
`infusion is not less than 2 mg of iron per mL and administer over at least 15 minutes.
`
`When added to an infusion bag containing 0.9% sodium chloride injection, USP, at
`concentrations ranging from 2 mg to 4 mg of iron per mL, Injectafer solution is
`physically and chemically stable for 72 hours when stored at room temperature. To
`maintain stability, do not dilute to concentrations less than 2 mg iron/mL.
`
`Inspect parenteral drug products visually for the absence of particulate matter and
`discoloration prior to administration. The product contains no preservatives. Each vial of
`Injectafer is intended for single-dose only.
`
`When administering as a slow intravenous push, give at the rate of approximately 100 mg
`(2 mL) per minute. Avoid extravasation of Injectafer since brown discoloration of the
`extravasation site may be long lasting. Monitor for extravasation. If extravasation
`occurs, discontinue the Injectafer administration at that site.
`
`Discard unused portion.
`
`2.3 Repeat Treatment Monitoring Safety Assessment
`Injectafer treatment may be repeated if IDA reoccurs. Monitor serum phosphate levels in
`patients at risk for low serum phosphate who require a repeat course of treatment [see
`Warnings and Precautions (5.2)].
`
`
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`3
`•
`
`DOSAGE FORMS AND STRENGTHS
`Injection: 750 mg iron / 15 mL single-dose vial.
`
`CONTRAINDICATIONS
`4
`Injectafer is contraindicated in patients with a history of hypersensitivity to Injectafer or
`any of its components [see Warnings and Precautions (5.1)].
`
`
`WARNINGS AND PRECAUTIONS
`5
`5.1 Hypersensitivity Reactions
`Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which
`have been life-threatening and fatal, have been reported in patients receiving Injectafer.
`Patients may present with shock, clinically significant hypotension, loss of
`consciousness, and/or collapse. Monitor patients for signs and symptoms of
`hypersensitivity during and after Injectafer administration for at least 30 minutes and
`until clinically stable following completion of the infusion. Only administer Injectafer
`when personnel and therapies are immediately available for the treatment of serious
`hypersensitivity reactions. [see Adverse Reactions (6.1, 6.2)]. In clinical trials, serious
`anaphylactic/anaphylactoid reactions were reported in 0.1% (2/1775) of subjects
`receiving Injectafer. Other serious or severe adverse reactions potentially associated with
`hypersensitivity which included, but not limited to, pruritus, rash, urticaria, wheezing, or
`hypotension were reported in 1.5% (26/1775) of these subjects.
`
`5.2 Symptomatic Hypophosphatemia
`Symptomatic hypophosphatemia requiring clinical intervention has been reported in
`patients at risk of low serum phosphate in the postmarketing setting. These cases have
`occurred mostly after repeated exposure to Injectafer in patients with no reported history
`of renal impairment. Possible risk factors for hypophosphatemia include a history of
`gastrointestinal disorders associated with malabsorption of fat-soluble vitamins or
`phosphate, concurrent or prior use of medications that affect proximal renal tubular
`function, hyperparathyroidism, vitamin D deficiency and malnutrition. In most cases,
`hypophosphatemia resolved within three months.
`
`Monitor serum phosphate levels in patients at risk for low serum phosphate who require a
`repeat course of treatment. [see Dosage and Administration (2.3)].
`
`5.3 Hypertension
`In clinical studies, hypertension was reported in 3.8% (67/1,775) of subjects in clinical
`trials 1 and 2. Transient elevations in systolic blood pressure, sometimes occurring with
`facial flushing, dizziness, or nausea were observed in 6% (106/1,775) of subjects in these
`two clinical trials. These elevations generally occurred immediately after dosing and
`resolved within 30 minutes. Monitor patients for signs and symptoms of hypertension
`following each Injectafer administration [see Dosage and Administration (2)].
`
`5.4 Laboratory Test Alterations
`In the 24 hours following administration of Injectafer, laboratory assays may
`overestimate serum iron and transferrin bound iron by also measuring the iron in
`Injectafer.
`
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`ADVERSE REACTIONS
`6
`The following clinically significant adverse reactions are discussed in greater detail in
`other sections of the labeling:
`
` •
`
`Hypersensitivity Reactions [see Warnings and Precautions (5.1)]
`Hypophosphatemia [see Warnings and Precautions (5.2)]
`Hypertension [see Warnings and Precautions (5.3)]
`Laboratory Test Alterations [see Warnings and Precautions (5.4)]
`
`
`•
`•
`•
`
`6.1 Clinical Trials Experience
`Because clinical trials are conducted under widely varying conditions, the adverse
`reaction rates observed cannot be directly compared to rates in other clinical trials and
`may not reflect the rates observed in clinical practice.
`
`In two randomized clinical studies [Studies 1 and 2, see Clinical Studies (14)], a total of
`1,775 patients were exposed to Injectafer 15 mg/kg body weight up to a maximum single
`dose of 750 mg of iron on two occasions separated by at least 7 days up to a cumulative
`dose of 1500 mg of iron.
`
`Adverse reactions reported by ≥1% of treated patients are shown in the following table.
`
`Table 1. Adverse reactions reported in ≥1% of Study Patients in Clinical Trials 1 and 2
`
`Injectafer
`Pooled
`Oral
`
`
`Comparatorsa
`iron
`
`Term
`
`
`(N=1783)
`(N=1775)
`(N=253)
`%
`%
`%
`7.2
`1.8
`1.2
`Nausea
`3.8
`1.9
`0.4
`Hypertension
`3.6
`0.2
`0.0
`Flushing/Hot Flush
`2.1
`0.1
`0.0
`Blood Phosphorus Decrease
`2.0
`1.2
`0.0
`Dizziness
`1.7
`0.5
`0.4
`Vomiting
`1.4
`0.3
`0.0
`Injection Site Discoloration
`1.2
`0.9
`0.0
`Headache
`1.1
`0.2
`0.0
`Alanine Aminotransferase Increase
`1.1
`2.1
`0.0
`Dysgeusia
`1.0
`1.9
`0.0
`Hypotension
`0.5
`0.9
`3.2
`Constipation
`a Includes oral iron and all formulations of IV iron other than Injectafer
`
`Other adverse reactions reported by ≥0.5% of treated patients include abdominal pain,
`diarrhea, gamma glutamyl transferase increased, injection site pain/irritation, rash,
`paraesthesia, sneezing. Transient decreases in laboratory blood phosphorus levels (<2
`mg/dL) have been observed in 27% (440/1638) of patients in clinical trials.
`
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`6.2 Post-marketing Experience
`The following adverse reactions have been identified during post approval use of
`Injectafer. Because these reactions are reported voluntarily from a population of
`uncertain size, it is not always possible to reliably estimate their frequency or establish a
`causal relationship to drug exposure.
`
`The following adverse reactions have been reported from the post-marketing spontaneous
`reports with Injectafer:
`
` Cardiac disorders: Tachycardia
`• General disorders and administration site conditions: Chest discomfort, chills,
`pyrexia
`• Metabolism and nutrition disorders: Hypophosphatemia
`• Musculoskeletal and connective tissue disorders: Arthralgia, back pain,
`hypophosphatemic osteomalacia (rarely reported event)
`• Nervous system disorders: Syncope
`• Respiratory, thoracic and mediastinal disorders: Dyspnea
`Skin and subcutaneous tissue disorders: Angioedema, erythema, pruritus, urticaria
`•
`
` •
`
` 8
`
`USE IN SPECIFIC POPULATIONS
`
`8.1 Pregnancy
`
`Risk Summary
`Published studies on the use of ferric carboxymaltose in pregnant women have not
`reported an association with ferric carboxymaltose and adverse developmental outcomes.
`However, these studies cannot establish or exclude the absence of any drug-related risk
`during pregnancy because the studies were not designed to assess for the risk of major
`birth defects (see Data).
`
`There are risks to the mother and fetus associated with untreated IDA in pregnancy as
`well as risks to the fetus associated with maternal severe hypersensitivity reactions (see
`Clinical Considerations).
`
`In animal reproduction studies, administration of ferric carboxymaltose to rabbits during
`the period of organogenesis caused adverse developmental outcomes including fetal
`malformations and increased implantation loss at maternally toxic doses of approximately
`12% to 23% of the human weekly dose of 750 mg (based on body surface area).
`
`The estimated background risk of major birth defects and miscarriage for the indicated
`populations is unknown. Adverse outcomes in pregnancy occur regardless of the health
`of the mother or the use of medications. In the U.S. general population, the estimated
`background risk of major birth defects and miscarriage in clinically-recognized
`pregnancies is 2-4% and 15-20%, respectively.
`
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`
`Clinical Considerations
`
`Disease-associated maternal and/or embryo/fetal risk
`Untreated IDA in pregnancy is associated with adverse maternal outcomes such as post-
`partum anemia. Adverse pregnancy outcomes associated with IDA include increased risk
`for preterm delivery and low birth weight.
`
`Fetal/Neonatal adverse reactions
`Severe adverse reactions including circulatory failure (severe hypotension, shock
`including in the context of anaphylactic reaction) may occur in pregnant women with
`parenteral iron products (such as Injectafer) which may cause fetal bradycardia,
`especially during the second and third trimester.
`
`Data
`Human Data
`Published data from randomized controlled studies, prospective observational studies and
`retrospective studies on the use of ferric carboxymaltose in pregnant women have not
`reported an association with ferric carboxymaltose and adverse developmental outcomes.
`However, these studies cannot establish or exclude the absence of any drug-related risk
`during pregnancy because of methodological limitations, including that the studies were
`not primarily designed to capture safety data nor designed to assess the risk of major birth
`defects. Maternal adverse events reported in these studies are similar to those reported
`during clinical trials in adult males and non-pregnant females [see Adverse Reactions
`(6.1)].
`
`Animal Data
`Administration of ferric carboxymaltose to rats as an one-hour intravenous infusion up to
`30 mg/kg/day iron on gestation days 6 to 17 did not result in adverse embryonic or fetal
`findings. This daily dose in rats is approximately 40% of the human weekly dose of
`750 mg based on body surface area. In rabbits, ferric carboxymaltose was administered
`as a one-hour infusion on gestation days 6 to 19 at iron doses of 4.5, 9, 13.5, and 18
`mg/kg/day. Malformations were seen starting at the daily dose of 9 mg/kg (23% of the
`human weekly dose of 750 mg). Spontaneous abortions occurred starting at the daily
`iron dose of 4.5 mg/kg (12% of the human weekly dose based on body surface area).
`Pre-implantation loss was at the highest dose. Adverse embryonic or fetal effects were
`observed in the presence of maternal toxicity.
`
` pre- and post-natal development study was conducted in rats at intravenous doses up to
`18 mg/kg/day of iron (approximately 23% of the weekly human dose of 750 mg on a
`body surface area basis). There were no adverse effects on survival of offspring, their
`behavior, sexual maturation or reproductive parameters.
`
`
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`8.2 Lactation
`Risk Summary
`The available published data on the use of ferric carboxymaltose in lactating women
`demonstrate that iron is present in breast milk. However, the data do not inform the full
`potential exposure of iron for the breastfed infant. Among the breastfed infants, there
`were no adverse events reported that were considered related to ferric carboxymaltose
`exposure through breastmilk. There is no information on the effects of ferric
`carboxymaltose on milk production. The developmental and health benefits of
`breastfeeding should be considered along with the mother’s clinical need for Injectafer in
`addition to any potential adverse effects on the breastfed child from the drug or from the
`underlying maternal condition.
`
`Clinical Considerations
`Monitor breastfed infants for gastrointestinal toxicity (constipation, diarrhea).
`
`8.4 Pediatric Use
`Safety and effectiveness have not been established in pediatric patients.
`
`8.5 Geriatric Use
`Of the 1775 subjects in clinical studies of Injectafer, 50% were 65 years and over, while
`25% were 75 years and over. No overall differences in safety or effectiveness were
`observed between these subjects and younger subjects, and other reported clinical
`experience has not identified differences in responses between the elderly and younger
`patients, but greater sensitivity of some older individuals cannot be ruled out.
`
`10 OVERDOSAGE
`Excessive dosages of Injectafer may lead to accumulation of iron in storage sites
`potentially leading to hemosiderosis. A patient who received Injectafer 18,000 mg over 6
`months developed hemosiderosis with multiple joint disorder, walking disability, and
`asthenia. Hypophosphatemic osteomalacia was reported in a patient who received
`Injectafer 4000 mg over 4 months. Partial recovery followed discontinuation of Injectafer.
`
`DESCRIPTION
`11
`Ferric carboxymaltose, an iron replacement product, is an iron carbohydrate complex
`with the chemical name of polynuclear iron (III) hydroxide 4(R)-(poly-(1→4)-O-α-D-
`glucopyranosyl)-oxy-2(R),3(S),5(R),6-tetrahydroxy-hexanoate. It has a relative
`molecular weight of approximately 150,000 Da corresponding to the following empirical
`formula:
`
`[FeOx(OH)y(H2O)z]n [{(C6H10O5)m (C6H12O7)}l]k,
`
`where n ≈ 103, m ≈ 8, l≈ 11, and k ≈ 4
`(l represents the mean branching degree of the ligand).
`
`The chemical structure is presented below:
`
`
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`Reference ID: 4668211
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`
`
`
`Injectafer (ferric carboxymaltose injection) is a dark brown, sterile, aqueous, isotonic
`colloidal solution for intravenous injection. Each mL contains 50 mg iron as ferric
`carboxymaltose in water for injection. Injectafer is available in 15 mL single-dose vials.
`Sodium hydroxide and/or hydrochloric acid may have been added to adjust the pH to 5.0-
`7.0.
`
`Vial closure is not made with natural rubber latex.
`
`CLINICAL PHARMACOLOGY
`12
`12.1 Mechanism of Action
`Ferric carboxymaltose is a colloidal iron (III) hydroxide in complex with carboxymaltose,
`a carbohydrate polymer that releases iron.
`
`12.2 Pharmacodynamics
`Using positron emission tomography (PET) it was demonstrated that red cell uptake of
`59Fe and 52Fe from Injectafer ranged from 61% to 99%. In patients with iron deficiency,
`red cell uptake of radio-labeled iron ranged from 91% to 99% at 24 days after Injectafer
`dose. In patients with renal anemia, red cell uptake of radio-labeled iron ranged from
`61% to 84% at 24 days after Injectafer dose.
`
`12.3 Pharmacokinetics
`After administration of a single dose of Injectafer of 100 to 1000 mg of iron in iron
`deficient patients, maximum iron concentration of 37 µg/mL to 333 µg/mL were obtained
`respectively after 15 minutes to 1.21 hours post dose. The volume of distribution was
`estimated to be 3 L.
`
`The iron injected or infused was rapidly cleared from the plasma, the terminal half-life
`ranged from 7 to 12 hours. Renal elimination of iron was negligible.
`
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`CLINICAL STUDIES
`
`NONCLINICAL TOXICOLOGY
`13
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`Carcinogenicity studies have not been performed with ferric carboxymaltose.
`
`Ferric carboxymaltose was not genotoxic in the following genetic toxicology studies: in
`vitro microbial mutagenesis (Ames) assay, in vitro chromosome aberration test in human
`lymphocytes, in vitro mammalian cell mutation assay in mouse lymphoma
`L5178Y/TK+/- cells, in vivo mouse micronucleus test at single intravenous doses up to
`500 mg/kg.
`
`In a combined male and female fertility study, ferric carboxymaltose was administered
`intravenously over one hour to male and female rats at iron doses of up to 30 mg/kg.
`Animals were dosed 3 times per week (on Days 0, 3, and 7). There was no effect on
`mating function, fertility or early embryonic development. The dose of 30 mg/kg in
`animals is approximately 40% of the human dose of 750 mg based on body surface area.
`
`14
`
`14.1 Trial 1: Iron Deficiency Anemia in Patients Who Are Intolerant to Oral Iron or
`Have Had Unsatisfactory Response to Oral Iron
`
`The safety and efficacy of Injectafer for treatment of IDAwere evaluated in two
`randomized, open-label, controlled clinical trials (Trial 1 and Trial 2). In these two trials,
`Injectafer was administered at a dose of 15 mg/kg body weight up to a maximum single
`dose of 750 mg of iron on two occasions separated by at least 7 days up to a cumulative
`dose of 1500 mg of iron.
`
`Trial 1: A Multi-center, Randomized, Active Controlled Study to Investigate the Efficacy
`and Safety of Intravenous Ferric Carboxymaltose (FCM) in Patients with Iron Deficiency
`Anemia (IDA), (NCT00982007) was a randomized, open-label, controlled clinical study
`in patients with IDA who had an unsatisfactory response to oral iron (Cohort 1) or who
`were intolerant to oral iron (Cohort 2) during the 14-day oral iron run-in period.
`Inclusion criteria prior to randomization included hemoglobin (Hb) <12 g/dL, ferritin
`≤100 ng/mL or ferritin ≤300 ng/mL when transferrin saturation (TSAT) ≤30%. Cohort 1
`subjects were randomized to Injectafer or oral iron for 14 more days. Cohort 2 subjects
`were randomized to Injectafer or another IV iron per standard of care [90% of subjects
`received iron sucrose]. The mean age of study patients was 43 years (range, 18 to 94);
`94% were female; 42% were Caucasian, 32% were African American, 24% were
`Hispanic, and 2% were other races. The primary etiologies of IDA were heavy uterine
`bleeding (47%) and gastrointestinal disorders (17%).
`
`Table 2 shows the baseline and the change in hemoglobin from baseline to highest value
`between baseline and Day 35 or time of intervention.
`
`
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`Reference ID: 4668211
`
`Baseline
`
`
`
`Table 2. Mean Change in Hemoglobin From Baseline to the Highest Value
`Between Day 35 or Time of Intervention (Modified Intent-to-Treat Population)
`Hemoglobin (g/dL)
`Cohort 1
`Cohort 2
`Mean (SD)
`Injectafer
`Oral Iron
`Injectafer
`(N=244)
`(N=251)
`(N=245)
`10.6 (1.0)
`10.6 (1.0)
`9.1 (1.6)
`
`
`
`
`
`
`12.2 (1.1)
`11.4 (1.2)
`12.0 (1.2)
`
`
`
`
`
`
`1.6 (1.2)
`0.8 (0.8)
`2.9 (1.6)
`
`
`
`
`
`
`IV SCa
`(N=237)
`9.0 (1.5)
`
`
`11.2 (1.3)
`
`
`2.2 (1.3)
`
`
`
`0.001
`
`
`Highest Value
`
`
`
`Change (from baseline to
`highest value)
`
`0.001
`p-value
`SD=standard deviation; a: Intravenous iron per standard of care
`
`Increases from baseline in mean ferritin (264.2 ± 224.2 ng/mL in Cohort 1 and 218.2 ±
`211.4 ng/mL in Cohort 2), and transferrin saturation (13 ± 16% in Cohort 1 and 20 ±
`15% in Cohort 2) were observed at Day 35 in Injectafer-treated patients.
`
`14.2 Trial 2: Iron Deficiency Anemia in Patients with Non-Dialysis Dependent
`Chronic Kidney Disease
`
`Trial 2: REPAIR-IDA, Randomized Evaluation of efficacy and safety of Ferric
`carboxymaltose in Patients with Iron Deficiency Anemia and Impaired Renal function,
`(NCT00981045) was a randomized, open-label, controlled clinical study in patients with
`non-dialysis dependent chronic kidney disease. Inclusion criteria included hemoglobin
`(Hb) ≤11.5 g/dL, ferritin ≤100 ng/mL or ferritin ≤300 ng/mL when transferrin saturation
`(TSAT) ≤30%. Study patients were randomized to either Injectafer or Venofer. The
`mean age of study patients was 67 years (range, 19 to 101); 64% were female; 54% were
`Caucasian, 26% were African American, 18% Hispanics, and 2% were other races.
`
`Table 3 shows the baseline and the change in hemoglobin from baseline to highest value
`between baseline and Day 56 or time of intervention.
`
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`Reference ID: 4668211
`
`Table 3. Mean Change in Hemoglobin From Baseline to the Highest Value
`Between Baseline and Day 56 or Time of Intervention (Modified Intent-to-Treat
`Population)
`Hemoglobin (g/dL)
`Mean (SD)
`
`Injectafer
`(N=1249)
`
`Venofer
`(N=1244)
`
`Baseline
`
`Highest Value
`
`Change (from baseline to highest
`value)
`Treatment Difference (95% CI)
`
`10.3 (0.8)
`
`10.3 (0.8)
`
`11.4 (1.2)
`
`1.1 (1.0)
`
`11.3 (1.1)
`
`0.9 (0.92)
`
`0.21 (0.13, 0.28)
`
`Increases from baseline in mean f erritin (734.7 ± 337.8 ng/mL), and transferrin
`saturation (30 ± 17%) were observed prior to Day 56 in Injectafer-treated patients.
`
`16
`
`HOW SUPPLIED/STORAGE AND HANDLING
`
`NDC 0517-0650-01
`NDC 0517-0650-02
`
`Individually boxed
`750 mg iron/15 mL Single-Dose Vial
`750 mg iron/15 mL Single-Dose Vial Packages of 2
`
`Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to
`86°F). [See the USP controlled room temperature]. Do not freeze.
`
`PATIENT COUNSELING INFORMATION
`17
`Prior History of Reactions to Parenteral Iron Products
`Question patients regarding any prior history of reactions to parenteral iron products [see
`Warnings and Precautions (5.1)].
`
`Serious Hypersensitivity Reactions
`Advise patients to report any signs and symptoms of hypersensitivity that may develop
`during and following Injectafer administration, such as rash, itching, dizziness,
`lightheadedness, swelling and breathing problems [see Warnings and Precautions (5.1)].
`
`Injectafer is manufactured under license from Vifor (International) Inc, Switzerland.
`
`AMERICAN
`REGENT, INC.
`SHIRLEY, NY 11967
`
`RQ1052-C
`
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`Reference ID: 4668211
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`Patient Information
`INJECTAFER (in-jekt-a-fer)
`(ferric carboxymaltose injection)
`
`What is INJECTAFER?
`INJECTAFER is a prescription iron replacement medicine used to treat iron deficiency anemia (IDA) in adults who
`have:
`intolerance to oral iron or who have not responded well to treatment with oral iron, or
`•
`non-dialysis dependent chronic kidney disease
`•
`It is not known if INJECTAFER is safe and effective for use in children.
`Who should not receive INJECTAFER?
`Do not receive INJECTAFER if you are allergic to ferric carboxymaltose or any of the ingredients in INJECTAFER.
`See the end of this leaflet for a complete list of ingredients in INJECTAFER.
`Before receiving INJECTAFER, tell your healthcare provider about all of your medical conditions, including if
`you:
`have had an allergic reaction to iron given into your vein
`•
`have high blood pressure
`•
`are pregnant or plan to become pregnant. It is not known if INJECTAFER will harm your unborn baby.
`•
`are breastfeeding or plan to breastfeed. INJECTAFER passes into your breast milk. It is unknown whether
`•
`INJECTAFER would pose a risk to your baby. Talk to your healthcare provider about the best way to feed your
`baby during treatment with INJECTAFER.
`Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines,
`vitamins, and herbal supplements.
`How will I receive INJECTAFER?
`INJECTAFER is given intravenously (into your vein) by your healthcare provider in 2 doses at least 7 days apart.
`What are the possible side effects of INJECTAFER?
`INJECTAFER may cause serious side effects, including:
`• Allergic (hypersensitivity) reactions. Serious life-threatening allergic reactions have happened in people who
`receive INJECTAFER. Other serious reactions including itching, hives, wheezing, and low blood pressure also
`have happened during treatment with INJECTAFER. Tell your healthcare provider if you have ever had any
`unusual or allergic reaction to any iron given by vein.
`• High blood pressure (hypertension). High blood pressure, sometimes with face flushing, dizziness, or nausea,
`has happened during treatment with INJECTAFER. Your healthcare provider will check your blood pressure and
`check for any signs and symptoms of high blood pressure after you receive INJECTAFER.
`The most common side effects of INJECTAFER include:
`nausea
`high blood pressure
`•
`•
`flushing
`low levels of phosphorous in your blood
`•
`•
`dizziness
`•
`These are not all the possible side effects of INJECTAFER.
`Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
`General information about INJECTAFER
`Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can
`ask your pharmacist or healthcare provider for information about INJECTAFER that is written for health professionals.
`What are the ingredients in INJECTAFER?
`Active ingredient: ferric carboxymaltose
`Inactive ingredients: water for injection. Sodium hydroxide and/or hydrochloric acid may have been added to adjust
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`Reference ID: 4668211
`
`pH to 5.0-7.0.
`
`AMERICAN
`REGENT, INC.
`SHIRLEY, NY 11967
`
`For more information go to www.injectafer.com or call 1-800-734-9236.
`
`This Patient Information has been approved by the U.S. Food and Drug Administration.
`
`Revised: 9/2020
`
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